Author + information
- Received March 12, 2019
- Accepted April 29, 2019
- Published online July 8, 2019.
- Yang Sun, MDa,b,
- Yanghui Chen, MDb,
- Yuanyuan Li, MDb,
- Zongzhe Li, MD, PhDa,b,
- Chenze Li, MDb,
- Ting Yu, BNa,
- Lei Xiao, MDb,
- Bo Yu, MDb,
- Hu Zhao, MD, PhDa,
- Min Tao, BNa,
- Jiangang Jiang, MD, PhDa,b,
- Jiangtao Yan, MD, PhDa,b,
- Yan Wang, MD, PhDa,b,
- Hesong Zeng, MD, PhDa,b,
- Xiaoqing Shen, BNa,
- Yiwu Zhou, PhDc,
- Li Jin, PhDd,
- Weihua Song, MD, PhDe,
- Kefei Dou, MD, PhDe,∗∗ ( and )
- Dao Wen Wang, MD, PhDa,b,d,∗ (, )@HUST_China
- aDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- bHubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, China
- cDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- dCollaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
- eState Key Laboratory of Cardiovascular Disease, Department of Cardiology, Cardiovascular Institute, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- ↵∗Address for correspondence:
Dr. Dao Wen Wang, Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
- ↵∗∗Dr. Kefei Dou, Fuwai Hospital and National Center for Cardiovascular Diseases, Beijing 100037, China.
Background Spontaneous coronary artery dissection (SCAD) is defined as a splitting of the coronary artery wall exclusive of iatrogenesis or trauma. Since the last decades, our knowledge of the diagnosis and prognosis and therapy for SCAD has advanced; however, its causes remain unknown.
Objectives This study sought to identify genes associated with SCAD development in the Chinese Han population.
Methods Between November 2011 and January 2018, the authors enrolled 85 SCAD cases and 296 non-SCAD controls from the Chinese Han population. All 381 subjects enrolled underwent detection with whole exome sequencing, followed by Sanger sequencing for confirmation. Principle component analysis was used to evaluate the structure of the population. Haploview was used to analyze the linkage disequilibrium statistics of the variants. The author used 2 gene-based association tests, optimal sequence kernel association test and mixed effects score test, to identify the causal genes or variants of SCAD. Immunohistochemistry was used to detect the expression of TSR1 in coronary artery tissues.
Results Four genes with a suggestive association with SCAD (p < 5.41 × 10−5 in both the optimal sequence kernel association and mixed effects score tests) were identified, and TSR1 was the top hit. All TSR1 germline variants were either highly conserved across distinct species or lead to premature termination of protein syntheses. Furthermore, the expression of TSR1 was detectable in human coronary artery tissues.
Conclusions This study describes the clinical characteristics of the Chinese Han population with SCAD and identified TSR1 as a potential causal gene, which might bring about a further progress in diagnosis and treatment of the disorder.
This work was supported by projects Nature Science Foundation of China Nos. 91439203, 91839302, National Key R&D Program of China NO. 2017YFC0909400, and the fundamental Research Funds for the Central Universities, HUST NO. 2016JCTD117. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received March 12, 2019.
- Accepted April 29, 2019.
- 2019 American College of Cardiology Foundation